Circadian (3): The Power Wash
In 2011, I walked out of Newcastle University with the title of "Dr" before my name. The good old university did its best to train me to be worthy of that title, but they couldn’t have taught me what science had not yet discovered. In fact, the bulk of what was taught did not include the emerging research of the time; the university required years to reorganise its curriculum before including a new branch of any science. Even with significant funding from the pharmaceutical industry, I was still only reading studies on statins, for example, that were at least already six or seven years old.
In 2012, twelve brilliant researchers—half of whom are medical doctors—discovered a groundbreaking pathway in neuroscience that no one had been able to establish before. By experimenting with mice, they proved that our brains perform a "power wash" at night during NREM III sleep, famously described using the dishwasher metaphor. This is distinct from the "deep cleaning" we discussed in the last post, which happens constantly as long as glutathione is present. What I was taught in medical school was that cerebrospinal fluid (CSF) was produced in the ventricles at the center of the brain, flowed outward to the skull, and was absorbed into the blood vessels via the arachnoid granulations. At no point did the CSF actually enter the brain cells; it was merely a fluid cushioning the brain as it passed through the perivascular spaces known as Virchow-Robin spaces.
Following the 2012 findings, we now know that CSF enters the brain cells, cleanses them, and exits with waste products—much like how a dishwasher treats dirty dishes. Instead of being viewed as a "lifeless" space, these perivascular spaces have been elevated in importance and are now recognised as part of the "glymphatic system."
The following year, one of those researchers continued her journey to uncover the miracles that keep us alive despite our ignorance of them. Dr Maiken Nedergaard, along with her gifted associate Dr Lulu Xie, found that the brain actually shrinks by 60% when the glymphatics are most active. This was discovered after Dr Xie meticulously found a way to train mice to sleep under a microscope. This shrinkage allows for much more CSF to enter and perform that "power wash." It’s like having a moderately filled, evenly spaced load in the dishwasher rather than throwing the whole kitchen in and hoping everything comes out clean in the morning (which I’m sure some of us do!).
Believe it or not, most doctors who graduated before 2021 likely wouldn't have been taught the new syllabus incorporating the glymphatic system, which only began appearing around 2016. So, if your doctor looks young, don’t belittle their knowledge; instead, get ready for answers to questions other doctors have struggled to solve. Glymphatics is only one example. I have read countless studies dated after 2011 that have fundamentally changed my understanding of medicine and the human body. The key is staying up to date.
How does the brain shrink by that much during NREM III sleep? Let me help you with that. The real question is: how does the brain expand by 60% when we are awake? It expands because we produce noradrenaline as part of our "stay-awake" hormone response. When melatonin enters the scene, it makes the brain more sensitive to GABA. Melatonin and GABA work together to switch off noradrenaline. This is the "tug-of-war" between sleep and wakefulness happening in the background without any conscious instruction. When noradrenaline is tuned down—reaching a critically low level during NREM III—your brain is no longer as "large" as it needs to be when you are busy during the day.
I hope I’ve convinced you that maintaining a proper body clock is paramount to health. Referring back to our discussion on melatonin: your body must recognise the correct time for its production. Otherwise, you might "score" enough hours of sleep, but as the metaphor goes, the dishes remain dirty at the end of the cycle. What happens when the "dishes" stay dirty over time? We see all sorts of neurodegenerative diseases, most notably Alzheimer’s dementia.
It goes without saying that if you are a shift worker, your daytime sleep produces no melatonin. If you were to produce melatonin, it would have been while you were busy working. By the time you hit the pillow, you fall asleep simply due to the accumulation of adenosine—another player in the sleep-wake tug-of-war. Adenosine can nudge you into NREM I and II, but it does little for NREM III. Your noradrenaline continues to simmer, your brain remains "plump," and the power wash becomes ineffective. That is why, by the end of seven nights, you are desperate for a break before putting your body through another cycle of torture. You don’t need fancy science to know this; you just need to tap into how you feel after a night-shift roster to understand that this is not a sustainable plan for the body.